Human Tissue Act resource - Questions and Answers

The below questions were raised during the IDRN training event on the Human Tissue Act. These questions were submitted to the Human Tissue Authority, and they kindly provided the answers.

The 'answers' in italics were based on notes taken during the discussion sessions at the event. If these appear to be contradictory to the answers supplied by the Human Tissue Authority, then refer to the Authority's response in the first instance.

(The questions are in no particular order. Policy and procedures may change over time, so contact the Authority for an up-to-date position)

As researchers implement processes to meet the requirements of the license, it is important for them to know what precisely will be included in an HTA inspection so that suitable systems can be established from then start. When do the HTA intend to provide researchers with further details of inspections?

The HTA provides guidance to Designated Individuals (DIs) prior to inspection. The DI training days also include information on the inspection process.

The HTA excludes the need for a researcher to have a storage license if the research project has been approved by a UK ethics committee approved by UKECA, an NHS trust ,or recognised in accordance with the Part 2 of the Medicines for Human Use (Clinical Trials) Regulation 2004. Why does the HTA not give similar recognition to equivalent ethics committees overseas and thereby avoid additional research bureaucracy?

The Human Tissue Act 2004 (Ethical Approval, Exceptions from Licensing and Supply of Information about Transplants) Regulations produced by the Secretary of State set out exemptions to licensing. They allow that a licence is not required to store relevant material where it is stored for an ethically approved research project. These Regulations set out that the ethical approval must come from an ethics committee approved by UKECA to review clinical trials or a committee under the auspices of NRES (formally COREC). The Regulations do give any provision for the HTA to recognise ethics committees outside of the UK.

The list of Relevant Material appearing on the HTA website includes bodily waste to reflect the “possibility that even a single cell can be subject to research’. The majority of waste product are however not used for cellular research, but for analysis of other parameters eg drug levels. Why therefore are these listed as relevant materials?

The Act’s use of the words “…or includes human cells” in its explanation of what is considered to be relevant material suggests that Parliament meant it to be comprehensive. Hansard records a Ministerial statement that the term relevant material applied irrespective of the number of cells in the material. The Authority considered that a definition which reinforced this clear legislative intent was required. It noted that the Act did not attempt to limit or modify the scope of the need for consent according to the use to which the material was to be put or how it might be classified by those storing it or using it. In response to the suggestion from some commentators that bodily waste products containing cells might be exempted from relevant material status, the Authority took the view that the consent requirements stemming from relevant material status were entirely appropriate.

The Act refers to research scenarios where the researcher is not in possession of information from which the person from whose body the material has come can be identified. - see section 1 (9) b. Can the HTA please outline sample management processes that would meet these criteria?

Relevant material from the living may be stored for use and/or used without consent, provided that:

• the research is ethically approved
• the material is anonymised such that the researcher is not in possession of information identifying the person from whose body the material has come and is not likely to come into possession of it.

This does not mean that samples must be permanently and irrevocably unlinked – linking can be made through a third party where necessary e.g. a third party may anonymise the material and pass it on to the researcher. They may pass on further information to the researcher as required, as long as that information does not, or is not likely to, identify the person from whom the material came from.

However the HTA considers that it is always good practice to obtain consent to store and use relevant material for research.

If I wish to import sub-cellular human tissue into the UK for research, will this come under the HTA and if so what do I need to do to satisfy the regulations?

The definition of relevant material in the Human Tissue Act 2004 is ‘material that consists of, or includes cells’ therefore subcelluar material such as protein falls outside the HTA’s remit. However we are producing a Code of Practice on import and export of relevant material which gives guidance and you may wish to refer to this.

We have samples in storage pre Sept 2006, they have fulfilled the criteria for no license. However, if those samples are used now for research, do we need to apply for a license?

The consent provisions of the Human Tissue Act 2004 are not retrospective however this does not apply to the licensing provisions. Storage of relevant material for research other than a specific ethically approved project or a project pending approval requires a licence. There is no exemption for material collected prior to the Act coming into force. If you require a licence you should contact the HTA as soon as possible.

I believe that a moratorium on disposal of identifiable tissue samples was put in place after the Alder Hay scandal - with the Act now being law, has this moratorium been lifted and are there any specific requirements, such as contacting relatives, necessary before disposal of such material?

Are samples collected overseas covered by the Act? (pre and post-September 2006)

The consent provisions of the Human Tissue Act 2004 do not apply to imported material however the HTA will be issuing a Code of Practice on the Import and Export of human bodies, body parts and tissue shortly which will give guidance on this subject. This will be available on our website.

The licensing provisions of the Act do apply to imported material therefore storage of imported relevant material for research other than a specific ethically approved project or a project pending approval requires a licence.

Currently the Act only requires licensing for allogeneic cells, or autologous cells to be stored for longer than 48 hours. Culture and/or processing of cells may take longer than 48 hours. Furthermore, spare cells may be used for the purpose of development of cultural technique or further (laboratory) studies. Is a licence required in these cases?

The exemption from licensing for material stored for less than 48hrs only applies to material stored for transplantation.

Storage of relevant material for research other than a specific ethically approved project or a project pending approval requires a licence. Cell lines or cell cultures where none of the original cells are present are not considered as relevant material.

With wax-bedded blocks in retrospective studies, these can be anonymised, but can they be used without consent?

It is always good practice to obtain consent to use or store relevant material for research.

However you do not need consent to continue to store or use existing holdings (material collected prior 1 September 2006) for research.

Material collected from the living after 31 August 2006 may be stored for use and/or used without consent, provided that:

• the research is ethically approved
• the material is anonymised such that the researcher is not in possession of information identifying the person from whose body the material has come and is not likely to come into possession of it.

For rare genetic disorders or rare infectious diseases, the process of anonymisation isn’t always ideal, as there may be the need to trace the family history. What is best practice is this situation?

The Code of Practice on Consent (Code 1) and The removal, storage and disposal of human organs and tissues (Code5) provide guidance with regards to anonymisation of samples for the intended use is ethically approved research. It recognises that the origins of the relevant material may need to be traced in some instances, and suggests that consent for the removal, storage and use of the relevant material is taken to remove the need to implement complex system to ensure that samples remain unlinked. It is also recognised in Code 1 that obtaining consent for the relevant material to be used in your trial may also add benefit to facilitating the process of obtaining ethical approval.

This should be presented to the REC in a clear and concise manner. The HTA may impose restrictions upon the REC, hence the need for clarity when presenting the research proposal. This will certainly require informed consent from the patient (or relative if the patient is dead/incompetent). If the samples are being stored for possible research, then they should be stored is a licenced facility.

Diagnosis is not a scheduled purpose defined in the HT Act; therefore relevant material taken from the living and stored for this purpose is exempt from the licensing requirements.

If the relevant material is to be store following diagnostic procedures for further use in scheduled purposes, for example the research in connection with disorders or the functioning of the human body, then a licence will be required.

No, as this is specifically excluded from the Act. A licence is only needed if these samples are subsequently used for research purposes.

All samples that contain even a single human cell are covered by the Act.

Yes, the Act’s use of the words “…or includes human cells” in its explanation of what is considered to be relevant material suggests that Parliament meant it to be comprehensive. Hansard records a Ministerial statement that the term relevant material applied irrespective of the number of cells in the material. The Authority considered that a definition which reinforced this clear legislative intent was required. It noted that the Act did not attempt to limit or modify the scope of the need for consent according to the use to which the material was to be put or how it might be classified by those storing it or using it. In response to the suggestion from some commentators that bodily waste products containing cells might be exempted from relevant material status, the Authority took the view that the consent requirements stemming from relevant material status were entirely appropriate.

Who is deemed to be responsible if there is found to be levels of non-compliance with the Act? Is it the PI? Or all people working on those samples?

Under the Act the PI does not have a statutory role. Licensable activity is authorised to be carried out under the supervision of a Designated Individual, the HT Act defines the statutory duties of the DI:

- to ensure that all persons working under the licence are suitable to carry out the licensable activities
- to ensure that suitable practices are carried out under the licence
- to ensure that the conditions of the licence are complied with

Therefore the DI is responsible for ensuring all licensable activities are suitable. The DI in some cases may be the PI.

The donor would be required to provide consent for further use of the donated material in additional research purposes. Consent is not required if the samples are anonymised and to be used in an ethically approved research trial.

Ethical approval is required. The samples must be anonymised, and the protocol must state that these bloods can be used for research.

Consent is given on behalf of a child for a sample(s) to be used for research purposes. What are the implications if that sample is still being used when the child reaches the age of consent?

The Act defines a child as being under 18 years old. However a child can be considered competent to give valid consent if they have sufficient intelligence and understanding to enable them to fully understand what is involved (as defined in the Gillick case). A competent person can withdraw consent at any time.

There is no requirement to go back to obtain the consent of a child that is now competent to consent. However if they choose to withdraw consent there wishes should be followed. If consent is withdrawn, it is not necessary to remove the information that may have already been created as part of the research project – however best practice dictates that the wishes of the patient should be met.

When a child reaches the age of consent, they can withdraw their permission for the sample to continue to be used. Otherwise, the previously-obtained consent still applies.

We are collaborating with an institution that has a licence from the Authority. Do we need a licence to obtain samples from them?

The licensing requirement will depend on the purpose the material is stored for. Storage of relevant material requires a licence unless it is stored for a specific ethically approved research project.

We would also expect you to have a material transfer agreement with the licensed establishment to ensure that the relevant material is being stored / used / disposed of in accordance with the consent given.

No, in this case, a licence would only be needed if storing samples for future unspecified research.

If the material have being storage for the use in scheduled purposes then a licence may be required.

If the relevant material is being stored to be used a part of a specific ethically approved trial, the storage is exempt from licensing requirements. If you wish to store the relevant material following the end of the ethically approved trial a licence will be required.

If the samples are used for a current piece of research, then consent and ethical approval is all that is required. If the samples are to be used for a future piece of research, then a licence and further ethical approval are required.

Education or training relating to public health is a scheduled purpose. If the relevant material was obtained from the deceased and is being stored for this purpose then a licence is required. If the samples are open to view by the general public then you are required to obtain a licence for public display.

A public display licence may be required (contact the Authority). A storage licence would definitely be required.

In relation to criminal proceedings e.g. a murder case, when forensic examination of human material has been completed, what should happen to the samples then?

The coroner is required to obtain the wishes with regards to disposal or further use of material following a post mortem as part of their inquest. This is defined in The Coroner (Amendment) Rules 2005.

The Coroner should then inform the establishment storing the material to ensure that the wishes are met.

Once the Coroners case finishes the samples will need to be stored on licensed premises.

When the coroner closes the case, his authority stops. The coroner should in theory ask relatives for consent to keep the samples. This procedure is not covered by the Act. If the samples are to be used elsewhere, then consent is required, but a licence is not. If the samples are being held on instruction by the CPS, then this is exempt from the Act.

We have post-mortem tissue taken pre-September 2006. What should we do with this?

If you are holding relevant material that was removed before the 1 September 2006, you are not required to obtain consent for its storage, use or disposal, however you are still required to have a licence to store the material.

If the views of the deceased or their relatives are known, they must be reflected.

The HTA Code of Practice The removal, storage and disposal of human organs and tissue (Code 5) states that as good practice your organisation should develop local policies describing the criteria for disposal / further storage of relevant material and the frequency of review of relevant material being held. The policies should reflect the duty to donors – ensuring that donations are used whenever possible and suitable arrangements are in place to stop material being stored for no reason.

If samples are identifiable, but the relatives have not made contact, the samples should be kept for at least a year. If they have identifiable purpose, then can be kept for longer. If the samples are of no further use, they can then be disposed of.